None listed
Conditions
Brief summary
Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of aggressive Non-Hodgkin Lymphoma (NHL), accounting for 30-40% of all NHL cases. To assess the risk for DLBCL, doctors use tools like the International Prognostic Index (IPI), aaIPI, and NCCN-IPI. These tools help identify high-risk patients but are not good at spotting those at "ultra-high-risk" (UHR) of treatment failure within two years of diagnosis. The NHL34 CLARIFY-PROGNOSTIC study is a nationwide platform that offers real-time, centralized risk assessment for patients with Large B Cell Lymphoma (LBCL) who are treated with frontline immunochemotherapy. This may help doctors make better treatment decisions, provide more accurate prognoses, and advance molecular and imaging techniques in Australia and New Zealand. The study also aims to identify ultra high-risk LBCL patients for clinical trials of new treatments, creating an efficient and cost-effective framework for future lymphoma trials. Who is it for? You may be eligible for this study if you are 18 or older and have been diagnosed with LBCL. Study Details LBCL patients will commence standard of care immunotherapy regimen. They will have a FDG/PET scan and/or a MRD assay at baseline, cycle 4, cycle 6, and 3 months after treatment ends. A positive disease will be based on centralized baseline tumor sequencing, centralized delta standardized uptake value (SUV) quantification / Deauville score, and measurable residual disease (MRD) testing. These patients will be referred to relevant therapeutic arms of this study, dependent on meeting relevant criteria. A UHR LBCL patient population will be identified and referred to a relevant therapuetic arm of this study to test novel treatments such as CAR-T cell infusion. This research aims to evaluate the feasibility of achieving faster turnaround rates for centralized MRD and FDG-PET reviews, to identify an UHR population to get them on appropriate treatment sooner. By meeting the following benchmarks in real time, the study will significantly contribute to the field by enhancing the speed and accuracy of prognostic processes: • MRD analysis and report turnaround must be completed within 21 days from sample collection. • FDG-PET scan reports must be ready within 7 days for SUV/Deauville score at C4D15, C6D15, and 3 months after the end of treatment.
Interventions
The NHL34 CLARIFY study is a multi-domain platform trial. This master protocol aims to offer real-time, centralized risk assessment for patients with Large B Cell Lymphoma (LBCL) who are treated with standard of care (SOC) immunotherapy. Patients will receive SOC regardless of the registration of this centralised and risk assessment platform trial.
Patients will have a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan and a Measurable Residual Disease (MRD) assay at baseline, c
The NHL34 CLARIFY study is a multi-domain platform trial. This master protocol aims to offer real-time, centralized risk assessment for patients with Large B Cell Lymphoma (LBCL) who are treated with standard of care (SOC) immunotherapy. Patients will receive SOC regardless of the registration of this centralised and risk assessment platform trial. Patients will have a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan and a Measurable Residual Disease (MRD) assay at baseline, cycle 4, cycle 6, and 3 months after treatment ends. Disease risk assessment will be determined based on centralised baseline tumour sequencing, centralised delta standardized uptake value (SUV) quantification / Deauville score and Measurable Residual Disease (MRD) by phased-variant ctDNA sequencing (PVSeq) at the specified serial time points. The PVSeq limit of detection (LOD) is approximately 1 part per 1,000,000. Outcomes of the dynamic biomarker assessment will be provided to the treating clinician in real-time by a standardised report from the coordinating central laboratory to inform of disease risk assessment and guide subsequent management. This platform study will form the basis for patient screening and identify an ultra-high-risk (UHR) population. A weekly centralised review by the CLARIFY Prognostic Reference Committee (CPRC) meeting will occur to assess patient's eligibility to therapeutic treatment domains based on PVSeq assay and FDG-PET delta SUV / Deauville score. Patients who do not meet the criteria for a specific domain will be referred back to the master protocol. Patients suitable for a therapeutic intervention from the NHL34 platform study must fulfill the eligibility criteria for the specific intervention. Futility/failure of a treatment arm will be considered by the trial management committee and the ALLG safety and data monitoring committee in the event of any of the following: 1. Inadequate recruitment 2. Unacceptable toxicity 3. Evidence becoming available during the accrual phase of the trial, which clearly demonstrates that it is unethical to allocate patients to trial arms. The trial management committee will meet quarterly and the Safety and Data Monitoring Committee will review the patients registered to this platform annually. The pharmacological investigational products for therapeutic arms will be selected based on a multi-tiered evaluation process designed to ensure scientific validity, participant safety, and regulatory compliance. The selection criteria includes scientific rationale, preclinical evidence, regulatory and ethical review. A CLARIFY working group, that consists of haematologists and research specialists, will meet quarterly to discuss potential therapeutic arms. Interventions may include: -CAR-T cell therapy (e.g. Axicabtagene Ciloleucel), -Bispecific antibodies Overall Study Duration. Recruitment period: 2 years. Participant follow-up: 24 months post end-of-induction (EoI). Total study duration: Approximately 5 years.
Sponsors
Australasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed diagnosis of CD20 positive large B cell lymphoma including diagnosis by 2022 WHO classification: • DLBCL, not otherwise specified (NOS) including transformation from indolent lymphoproliferative disease • T-cell/histiocyte-rich large B-cell lymphoma • Epstein-Barr virus-positive DLBCL, NOS • DLBCL/HGBCL with MYC and BCL2 rearrangements • High-Grade B-Cell Lymphoma (HGBCL), NOS • Follicular Large B Cell Lymphoma (FLBCL) (previously Grade 3B Follicular Lymphoma) • High-risk pretreatment clinical prognostication by either • Patients greater than 60-years: IPI Score greater than 3 • Patients less than 60-years: aaIPI Score 2-3 • Planned for frontline treatment with minimum 6 cycles of a combined immunochemotherapy regimen containing rituximab and anthracycline. These include: R-CHOP, DA-R-EPOCH, R-CHEOP, R-CHEP, R-Hyper-CVAD, Pola-R-CHP. Additional regimens may be approved on discussion with Co-PI 3. Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 4. Ability to provide tumour tissue; archival or freshly collected 5. Aged greater than 18 years old at the time of screening 6. Life expectancy (due to non-lymphoma related reasons) of at least 6-months 7. Available for follow-up for 2-years post EoT 8. Can provide written informed consent
Exclusion criteria
1. Histological subtypes of LBCL including mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites; primary effusion DLBCL; primary cutaneous DLBCL, leg type; Post-Transplant Lymphoproliferative Disease 2. Primary or secondary CNS lymphoma at the time of recruitment to the study 3. Prior therapy for lymphoproliferative disease, with the exception of: a. Corticosteroids (100mg or equivalent for less than 14 days) b. Radiotherapy to target lesions as consolidation is allowed provided intent and anatomical location of consolidative radiotherapy is prespecified prior to or at enrolment. Radiation prior to enrolment is not permitted. c. Central Nervous System (CNS) Prophylaxis (intrathecal or high-dose methotrexate) may be provided at treating clinician discretion as per local guidelines. 4. Pregnancy or lactation 5. Active synchronous solid tumour malignancy (excluding non-melanoma skin cancers and localised renal cell carcinoma) 6. Severe active infection. 7. Has any other clinically important abnormalities as determined by the recruiting investigator that may interfere with participation in or compliance with the study. 8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent to the trial.
Outcome results
None listed